Plinear Trend Research Articles

Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study.

Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40-78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.

Retinopathy of Prematurity and Glucose-6-Phosphate Dehydrogenase Activity: A Case-Control Study.

To determine whether red blood cell glucose-6-phosphate dehydrogenase (G6PD) activity is associated with retinopathy of prematurity (ROP). This case-control study was conducted in a Level-3 neonatal unit. Subjects were inborn boys with birth weight <2000g. "Cases" were consecutive subjects with ROP of any severity. "Controls" were consecutive unrelated subjects without ROP. Recipients of blood or exchange transfusions were excluded. Sixty cases (out of 98 screened) and 60 controls (out of 93 screened) were enrolled. G6PD activity (quantitative assay) as the candidate risk factor was evaluated. Sixty cases with 60 controls [mean (SD) gestation 28.80 (2.2) and 30.60 (2.2) wk respectively] were compared. "Cases" had a higher median (1st, 3rd quartile) G6PD activity compared to "controls" [7.39 (4.7, 11.5) vs. 6.28 (4.2,8.8) U/g Hb, p = 0.084]. G6PD activity was highest among ROP requiring treatment [8.68 (4.7, 12.3)] followed by ROP not requiring treatment [6.91 (4.4, 11.0)], followed by controls (plinear trend = 0.06). Gestation, birth weight, duration of oxygen, breastmilk feeding, and clinical sepsis were other variables associated with ROP on univariable analysis. On multivariable logistic regression, G6PD activity [Adjusted OR 1.14 (1.03, 1.25), p = 0.01] and gestation [Adjusted OR 0.74 (0.56, 0.97), p = 0.03] independently predicted ROP. C-statistic of the model was 0.76 (95% CI 0.67, 0.85). Higher G6PD activity was independently associated with ROP after adjusting for confounders. Each 1 U/g Hb increase in G6PD increased the odds of ROP by 14%. Severer forms of ROP were associated with higher levels of G6PD activity.

Abstract P415: Trends in Ultra-Processed Food Intake by Supplemental Nutrition Assistance Program Participation in the U.S.

Introduction: The Supplemental Nutrition Assistance Program (SNAP) plays an important role in shaping the diet of low-income individuals and families. Trends in ultra-processed food intake (UPF) among SNAP participants and non-participants has not been studied. Hypothesis: Compared to non-participants, SNAP participants would have a higher UPF intake; purchases would be larger for foods from SNAP-eligible versus ineligible venues. Methods: Data from NHANES survey cycles 2003-2004 through 2017-2018 were used. Dietary recalls from individuals ≥1 year of age were categorized according to Nova classification. Venues from which individuals reported buying food were grouped as SNAP-eligible (ex. grocery/supermarkets, convenience stores) or SNAP-ineligible venues (ex. restaurant/cafeteria). SNAP participation status was self-reported and categorized as SNAP participants; income-eligible nonparticipants (no SNAP + family income ≤130% of federal poverty line, FPL); lower-income, ineligible non-participants (no SNAP + family income &gt;130% - ≤300% of FPL); higher-income ineligible non-participants (no SNAP + family income &gt;300% FPL). UPF (% of total daily kcal) across eight survey cycles was examined using multivariable linear regression, stratified by SNAP participation status. Heterogeneous trends across SNAP participation status were tested by Wald F models. Trends were examined for UPF purchased from different venues. Analyses were conducted in youths (ages 1-19) and adults (≥ 20), separately. Results: The sample included 54979 participants from 2003-2004 through 2017-2018. The % of energy from UPF increased over time in both youth (Δ 2018-2003 , 4.3%; 95% CI, 2.9% - 5.8%; P linear trend &lt; .001) and adults (Δ 2018-2003 , 2.5%; 95% CI, 0.2% - 4.9%; P linear trend = .002). There were no differences between SNAP participants, income-eligible non-participants, lower-income ineligible and higher-income non-participants. The mean contribution of UPF from SNAP-eligible venues decreased in both youth (Δ 2018-2003 , -2.6%; 95% CI, -6.1% - 0.9%; P linear trend = .001) and adults (Δ 2018-2003 , -2.3%; 95% CI, -5.0% - 0.8%; P cubic trend &lt; .001) with no differences by SNAP participation. UPF purchases from fast-food restaurants increased in youth (Δ 2018-2003 , 2.2%; 95% CI, -0.4% - 4.8%; P quadratic trend = .036) and adults (Δ 2018-2003 , 2.9%; 95% CI, 0.6% - 5.1%; P cubic trend = .007), while those from schools remained unchanged. There were no differences by SNAP participation status. Conclusions: Total UPF consumption increased between 2003-2004 and 2017-2018 and were seen among both participants of SNAP and among income-eligible and ineligible non-participants. UPF were increasingly sourced from SNAP ineligible venues. SNAP benefit allotments should account for secular changes in dietary patterns by enabling the purchase of healthier processed and prepared foods.

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study.

Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR]=0.87, 95% confidence interval [CI]=0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR=0.70, 95% CI=0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend=0.02). There was no association for hydrophilic statins. Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Urine 24-Hour Sodium Excretion Decreased between 1953 and 2014 in Japan,but Estimated Intake Still Exceeds the WHO Recommendation

Background: Accurate monitoring of sodium intake is necessary for evaluating strategies used to reduce sodium intake. However, no repeat survey has been conducted in representative populations in Japan to examine trends in sodium intake with the use of 24-h urinary sodium excretion, a standard evaluation method for sodium intake monitoring.Objective: The objective of this study was to examine potential trends in sodium intake by examining previous reports of 24-h urinary sodium excretion in healthy Japanese adult populations.Methods: We systematically searched for reports of 24-h urinary sodium excretion in healthy Japanese adult populations (mean age range: 18-69 y). We searched PubMed and Web of Science for English-language articles and hand-searched 7 Japanese scientific journals for Japanese-language articles. Trends in urinary sodium excretion were examined with the use of weighted linear regression and random-effects meta-regression analyses, with adjustment or stratification to address study characteristics (population mean age, percentage of men, and sample size) and study assessment for completeness of urine collection.Results: We identified 68 reports of urinary sodium excretion from 53 articles published from 1953 through 2014 that showed high rates of urinary sodium excretion in healthy Japanese adult populations (weighted mean: 4900 mg/d). The rate of urinary sodium excretion significantly decreased between 1953 and 2014, by 4350 mg/d (P < 0.001); however, the rate of reduction in urinary sodium excretion was variable and decreased with time (P-linear trend <0.001 and P-quadratic trend <0.001). In the random-effects meta-regression analysis of studies that assessed completeness of urine collection with creatinine excretion, no significant relation between urinary sodium excretion and year was observed from 1978 to 2014 (β = -16, P = 0.40).Conclusion: Despite a decrease in urinary sodium excretion in healthy Japanese adult populations between 1953 and 2014, sodium intake still exceeds the WHO recommendation for adults. This review was registered at PROSPERO as CRD42016035452.

Trends in ethnic disparities in clinical cardiovascular health among Chinese adults from 2016–2020

Background and aimsLittle is known about the long-term trends in ethnic differences in cardiovascular health (CVH) in China in recent years. This study aimed to investigate ethnic differences in CVH and identify long-term trends in China. Methods and resultsThis survey was based on the physical examination data of Tacheng Prefecture in China from 2016 to 2020, and included 1,947,938 physical examination participants aged over 20 years for analysis. The American Heart Association (AHA) criteria were used to evaluate the clinical CVH of the subjects. The time trends from 2016 to 2020 were assessed using a weighted linear regression model stratified by ethnicity. The ethnic groups included Han, Kazakh, Hui, Mongolian, Uyghur, among others.The mean ideal clinical cardiovascular score was highest in Hui and lowest in Uyghur. The scores increased from 5.99 (5.95–6.03) to 6.11 (6.08–6.14) in Kazakh males and from 6.05 (5.99–6.11) to 6.11 (6.06–6.16) in Hui males among participants (Plinear trend < 0.001). The scores for the other groups declined significantly from 2016 to 2020(Plinear trend ＜ 0.05). In the sensitivity analysis, the trend remained unchanged after calculating the body mass index (BMI) cut-off for China. ConclusionClinical CVH differences still exist among different ethnic groups, with a decline in CVH from 2016 to 2020 in all except Kazakh and Hui males. This may indicate a higher incidence and poorer prognosis of cardiovascular disease in the future and can provide guidelines for improving CVH.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.

BACKGROUNDSingle-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS).AIMTo assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS.METHODSIn this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs — HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A — were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTSDepressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (Fdepressive = 7.475, Pdepressive = 0.006; Fanxiety = 6.535, Panxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSIONWe have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Increased vitamin B6 turnover is associated with greater mortality risk in the general US population: A prospective biomarker study

Vitamin B6 status and mortality risk are inversely associated in different patient groups, while prospective studies in the general population are lacking. Here, for the first time, we evaluated the association between biomarkers of vitamin B6 status and mortality risk in a large population-based study. The vitamin B6 vitamers pyridoxal-5'-phosphat (PLP) and 4-pyridoxic acid (4-PA) were measured by high-performance liquid chromatography in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. Participants' vital status and causes of death were recorded until December 2015. Multivariable Cox regression analyses were carried out to estimate Hazard Ratios (HRs) and 95% confidence intervals (CIs) of mortality across quintiles of PLP, 4-PA, and the ratio of 4-PA and PLP. Out of 15,304 study participants aged between 20 and 85 years at baseline, 1666 (7.7%) died during a median follow-up time of 7.8 years. An inverse association between PLP and mortality was found in a multivariable model adjusted for socioeconomic and lifestyle factors but became statistically non-significant upon adjustment for routine biomarkers (C-reactive protein, creatinine, albumin, and alkaline phosphatase). There was a significant linear trend for a positive association between 4-PA levels and mortality risk in the fully adjusted regression model, although a comparison of extreme quintiles (quintile 5 vs. quintile 1) did not show a significant difference (HRQ5vs.Q1 (95% CI): 1.19 (0.93, 1.51), plinear trend=0.02). A positive association between the 4-PA/PLP ratio and all-cause mortality was observed in the multivariable model, with an HRsQ5vs.Q1 of 1.45 (95% CI: 1.14, 1.85; plinear trend<0.0001). There were no significant associations between the biomarkers and cardiovascular or cancer mortality. The association between 4-PA/PLP and mortality risk was heterogeneous across age groups, and only statistically significant among participants older than 65 years at baseline (HRQ5vs.Q1 (95% CI): 1.72 (1.29, 2.29), plinear trend<0.0001). In this group, 4-PA/PLP was also associated with cancer mortality, with an HR Q5vs.Q1 of 2.16 (1.20, 3.90), plinear trend=0.02). Increased vitamin B6 turnover, as indicated by a higher 4-PA/PLP ratio, was associated with all-cause and cancer mortality among the older U.S. general population. Intervention trials are needed to assess whether older individuals with a high 4-PA/PLP ratio would benefit from increased vitamin B6 intake.

Quantile-Specific Heritability of Inflammatory and Oxidative Stress Biomarkers Linked to Cardiovascular Disease.

PurposeHeritability (h2, the proportion of the phenotypic variance attributable to additive genetic effects) is traditionally assumed to be constant throughout the distribution of the phenotype. However, the heritabilities of circulating C-reactive protein, interleukin-6, plasminogen activator inhibitor type-1 (PAI-1), and monocyte chemoattractant protein-1 (MCP-1) concentrations depend upon whether the phenotype is high or low relative to their distributions (quantile-dependent expressivity), which may account for apparent gene–environment interactions. Whether the heritabilities of other inflammatory biomarkers linked to cardiovascular disease are quantile-dependent remain to be determined.Patients and MethodsQuantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted phenotypes of families surveyed as part of the Framingham Heart Study. Quantile-specific heritabilities were calculated as: h2=2βOP/(1+rspouse) and h2={(1+8rspouseβFS)0.5–1}/(2rspouse).ResultsHeritability (h2 ± SE) of lipoprotein-associated phospholipase A2 (Lp-PLA2) mass concentrations increased from 0.11 ± 0.03 at the 10th percentile, 0.08 ± 0.03 at the 25th, 0.12 ± 0.03 at the 50th, 0.20 ± 0.04 at the 75th, and 0.26 ± 0.06 at the 90th percentile, or 0.0023 ± 0.0006 per each one-percent increase in the phenotype distribution (Plinear trend= 0.0004). Similarly, h2 increased 0.0029 ± 0.0011 (Plinear trend= 0.01) for sP-selectin, 0.0032 ± 0.0009 (Plinear trend= 0.0001) for soluble intercellular adhesion molecule 1 (sICAM-1), and 0.0026 ± 0.0006 for tumor necrosis factor receptor 2 (TNFR2) (Plinear trend= 5.0 × 10−6) per each one-percent increase in their distributions when estimated from βOP. Osteoprotegerin and soluble ST2 heritability also increased significantly with increasing percentiles of their distributions when estimated from βFS. Lp-PLA2 activity, CD40 ligand, TNFα, interleukin-18, and myeloperoxidase heritability showed no significant quantile-dependence.ConclusionThe heritabilities of circulating Lp-PLA2-mass, sP-selectin, sICAM-1, TNFR2, osteoprotegerin and soluble ST2 concentrations are quantile-dependent, which may contribute to purported genetic modulations of: 1) sP-selectin’s relationships to venous thrombosis, pulmonary hypertension, type 2 diabetes and atorvastatin treatment; 2) sICAM-I’s relationships to brain abscess and atorvastatin treatment; and 3) Lp-PLA2’s relationships to myocardial infarction and preeclampsia.

Quantile-specific heritability of monocyte chemoattractant protein-1, and relevance to rs1024611-disease interactions.

Monocyte chemoattractant protein-1 (MCP-1) concentrations are 34% to 47% heritable. Larger -2518 G/A (rs1024611) genotypes differences are reported for: 1) MCP-1 production in stimulated vs. basal cells; and 2) MCP-1 concentrations in diseased (sepsis, brain abscess, hepatitis B virus, Alzheimer's disease, Behcet's disease, and systemic lupus erythematosus) vs. healthy patients. Those results suggest that the -2518 G/A effect size may depend on whether the phenotype is high or low relative to its distribution (quantile-dependent expressivity). To test whether quantile-dependent expressivity applies more broadly to genetic influences on MCP-1 concentrations, quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted serum MCP-1 concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2=2βOP/(1+rspouse) and h2={(1+8rspouseβFS)0.5-1}/(2rspouse)). Heritability (h2±SE) of MCP-1 concentrations increased from 0.15±0.05 at the 10th percentile of the MCP-1 distribution, 0.23±0.04 at the 25th, 0.32±0.05 at the 50th, 0.43±0.07 at the 75th, and 0.44±0.07 at the 90th percentile, or an 0.0041±0.0009 increase for each one-percent increment in the MCP-1 distribution (Plinear trend=2.4×10-5) when estimated from βOP, and (Plinear trend=7.7×10-9) when estimated from βFS. Compared to the 10th percentile, βOP-estimated h2 was 3-fold greater at the 90th percentile (Pdifference=0.0003), and 6.9-fold greater when estimated from βFS (Pdifference=3.3×10-6). Re-analysis of in vivo comparison of MCP-1 concentrations in controls vs. patients with MCP-1-elevating conditions, and in vitro studies of MCP-1 production in basal vs. stimulated cells, show rs1024611 genotypes differences that were consistent with quantile-dependent expressivity. The heritability of circulating MCP-1 concentrations is quantile-dependent.

Quantile-specific heritability of 8-isoprostane and the modulating effects of smoking, alcohol, cardiovascular disease and diabetes on 8-isoprostane-gene interactions

BackgroundUrinary 8-isoprostane provides a significantly heritable measure of oxidative stress. Prior reports suggest that genetic variants may modulate oxidative stress due to smoking, other environmental factors, and disease. Alternatively, these apparent modulations may reflect a dependence of genetic effects on 8-isoprostane concentrations. MethodTo test whether genetic effects on 8-isoprostane concentrations are quantile-dependent, quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted creatinine-standardized urinary 8-isoprostane concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2 = 2βOP/(1+rspouse) and h2 = {(1+8rspouseβFS)0.5-1}/(2rspouse)). ResultsSpouse 8-isoprostane concentrations were weakly concordant (rspouse = 0.06). 8-isoprostane heritability (h2±SE) increased significantly with increasing percentiles of its distribution (Plinear trend = 0.0009, Pquadratic trend = 0.0007, Pcubic trend = 0.003) when estimated from βOP, and when estimated from βFS (Plinear trend = 0.005, Pquadratic trend = 0.09, Pcubic trend = 0.06). Compared to the 10th percentile, βOP-estimated h2 was over 22-fold greater at the 90th percentile (Pdifference = 9.2 × 10−5), and 5.3-fold greater when estimated from βFS (Pdifference = 0.004). Significantly higher 8-isoprostane heritability in smokers than nonsmokers (0.352 ± 0.147 vs. 0.061 ± 0.036, Pdifference = 0.01), and heavier than lighter drinkers (0.449 ± 0.216 vs. 0.078 ± 0.037, Pdifference = 0.01) were eliminated when corrected for the higher 8-isoprostane concentrations of the smokers and heavier drinkers. ConclusionHeritability of oxidative stress as measured by 8-isoprostane is quantile-dependent, which may contribute to the larger reported effects on oxidative stress by UCP2 -866G > A, IL6 -572C > G and LTA 252A > G polymorphisms in smokers than nonsmokers, by the UCP2 -866G > A polymorphism in coronary heart disease patients, by the ESRRG rs1890552 A > G polymorphism in type 2 diabetics, by the CYBA 242C > T polymorphism after exercise training, by the PLIN 11482G > A/14995A > T haplotype before weight loss, and by the CYBA -930A > G and GSTP1 I105V haplotypes in patients with pulmonary edema.

Trends and disparities in osteoarthritis prevalence among US adults, 2005\u20132018

Studies reporting trends and disparities of osteoarthritis (OA) in the United States are limited. We aimed to examine trends and disparities of OA prevalence among US adults, from 2005 to 2018. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2017–2018 were analyzed. Age-adjusted and self-reported OA prevalence, stratified by race/ethnicity and socioeconomic status (SES), was calculated separately for men and women. The linear trend and the association between the survey cycles and OA prevalence were assessed. Age-adjusted and self-reported OA prevalence linearly increased in the seven survey cycles (both Plinear trend ≤ 0.0002) in men and women. Non-Hispanic Caucasians (both Plinear trend ≤ 0.0001) in both genders and Non-Hispanic African Americans women (Plinear trend ≤ 0.0001) had significantly increasing linear trends in OA prevalence. In addition, people with lower SES had a lower age-adjusted prevalence of self-reported OA when compared to those with higher SES. The increasing linear trends still existed among both men and women after adjusting for multiple confounders (both Plinear trend ≤ 0.002). There were significant rising trends and disparities in self-reported OA prevalence among US men and women between 2005 and 2018.

Quantile‐specific heritability of plasminogen activator inhibitor type‐1 (PAI‐1, aka SERPINE1) and other hemostatic factors

BackgroundPlasminogen activator inhibitor type‐1 (PAI‐1, aka SERPINE1) is a moderately heritable glycoprotein that regulates fibrin clot dissolution (fibrinolysis). ObjectivesTest whether the heritabilities (h2) of PAI‐1 and other hemostatic factors are constant throughout their distribution or whether they are quantile‐specific (i.e., a larger or smaller h2 depending on whether their concentrations are high or low). MethodsQuantile regression was applied to 5606 parent‐offspring pairs and 5310 full siblings of the Framingham Heart Study. Quantile‐specific heritability was estimated from the parent‐offspring regression slope (βPO, h2 = 2βPO/(1+rspouse)) and the full‐sib regression slope (βFS, h2 = {(1+8rspouseβFS)0.5–1}/(2rspouse)). ResultsHeritability (h2 ± SE) increased significantly with increasing percentiles of the offspring's age‐ and sex‐adjusted PAI‐1 distribution when estimated from βPO (plinear trend = 0.0001): 0.09 ± 0.02 at the 10th, 0.09 ± 0.02 at the 25th, 0.16 ± 0.02 at the 50th, 0.29 ± 0.04 at the 75th, and 0.26 ± 0.08 at the 90th percentile of the PAI‐1 distribution, and when estimated from βFS (plinear trend = 6.5x10−7). There was no significant evidence for quantile‐specific heritability for factor VII (plinear trend = 0.35), D‐dimer (plinear trend = 0.08), tPA (plinear trend = 0.74), or von Willebrand factor (plinear trend = 0.79). ConclusionHigher mean plasma PAI‐1 antigen concentrations tend to accentuate genetic effects (quantile‐dependent expressivity), which is consistent with the greater reported differences in PAI‐1 concentrations between rs1799889 SERPINE1 (4G/5G) genotypes in patients with osteonecrosis, meningococcal sepsis, obesity, prior myocardial infarction, deep vein thrombosis, and polycystic ovarian syndrome than in healthy controls. It is also consistent with the greater increases in PAI‐1 concentrations in 4G‐allele carriers than 5G/5G homozygotes following fibrinolytic treatment, low‐salt intake, and high saturated fat intake.

861Mendelian randomization on habitual coffee intake and plasma lipid profile: evidence from UK Biobank

Abstract Background Long-term heavy coffee consumption may adversely affect individuals’ cardiovascular disease (CVD) risk. As hyperlipidemia is a well-established contributor to CVD, we investigated the association between habitual coffee intake and plasma lipid profile. Methods We used data from up to 362,571 UK Biobank participants to examine associations between coffee intake and plasma lipid profiles, including LDL-C, HDL-C, total-C, triglycerides, ApoA1 and ApoB. Inverse variance weighted mendelian randomization (MR) was used to interrogate the causal nature of coffee-lipid associations, complemented by pleiotropy-robust methods, including MR-median, MR-Mode, MR-PRESSO and MR-Egger. Results We observed positive dose-dependent associations between self-reported coffee intake and plasma concentration of LDL-C, ApoB and total-C, with the highest lipid levels seen among participants drinking &amp;gt;6 cups/day (Plinear trend≤1.97E-57 for all). Genetic instrument for coffee intake was robustly associated with self-reported intake in the UK Biobank (F-statistic = 416). One cup increase in genetically instrumented intake was associated with 0.07 mmol/L (95%CI 0.03 to 0.12), 0.02 g/L (95%CI 0.01 to 0.03), and 0.09 mmol/L (95%CI 0.04 to 0.14) increase in LDL-C, ApoB, and total-C, respectively. Pleiotropy-robust methods provided largely consistent results albeit with greater imprecision when using MR-Egger. Conclusions Our phenotypic and genetic analysis consistently suggests that long-term heavy coffee consumption can lead to unfavourable lipid profile, which could potentially increase individuals’ risk for CVD. Individuals with elevated cholesterol may need to reduce their daily coffee intake. Key messages Our study provides evidence that long-term heavy coffee consumption can lead to unfavourable lipid profile.

Trends in osteoporosis and mean bone density among type 2 diabetes patients in the US from 2005 to 2014

This study aimed to examine how bone health changed among T2DM patients in the past decade. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2013–2014 were analyzed to examine the trends of bone mineral density (BMD) and the prevalence trends of osteoporosis osteopenia among T2DM patients and non-diabetic people aged 40 years and older. The age- and BMI-adjusted mean BMD of the femur neck for the four NHANES cycles decreased linearly in both T2DM patients and non-diabetic people (both Plinear trend ≤ 0.009). Among women with T2DM, the mean BMD in 2013–2014 was significantly lower than that in 2005–2006, even after adjusting for multiple covariates. During 2005–2014, the prevalence of osteoporosis among T2DM patients and non-diabetic people increased but with no significant linear trend (both Plinear trend > 0.05), while the prevalence of osteopenia in the two populations increased linearly (both Plinear trend < 0.04). Age- and BMI-adjusted mean BMD decreased in 2013–2014 in patients with T2DM and non-diabetic people, while the prevalence of osteoporosis and osteopenia increased in both groups.

Habitual coffee intake and plasma lipid profile: Evidence from UK Biobank

There is evidence that long-term heavy coffee consumption may adversely affect individuals' cardiovascular disease (CVD) risk. As hyperlipidemia is a well-established contributor to CVD risk, we investigated the association between habitual coffee intake and plasma lipid profile. We used data from up to 362,571 UK Biobank participants to examine phenotypic associations between self-reported coffee intake and plasma lipid profiles, including low-density-lipoproteins cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (total-C), triglycerides, and apolipoproteins A1 and B (ApoA1 and ApoB). Mendelian randomization (MR) analysis using genetically instrumented coffee intake was used to interrogate the causal nature of coffee-lipid associations. We observed a positive dose-dependent association between self-reported coffee intake and plasma concentration of LDL-C, ApoB and total-C, with the highest lipid levels seen among participants reported drinking >6 cups/day (Plinear trend≤ 3.24E-55 for all). Consistently, in MR analyses using genetically instrumented coffee intake one cup higher coffee intake was associated with a 0.07mmol/L (95% CI 0.03 to 0.12), 0.02g/L (95% CI 0.01 to 0.03), and 0.09mmol/L (95% CI 0.04 to 0.14) increase in plasma concentration of LDL-C, ApoB, and total-C, respectively. Our phenotypic and genetic analyses suggest that long-term heavy coffee consumption may lead to unfavourable lipid profile, which could potentially increase individuals' risk for CVD. These findings may have clinical relevance for people with elevated LDL cholesterol.

Association of Milk Consumption and Vitamin D Status in the US Population by Ethnicity: NHANES 2001-2010 Analysis.

Vitamin D has been identified as a nutrient of public health concern, and higher intake of natural or fortified food sources of vitamin D, such as milk, are encouraged by the 2015–2020 Dietary Guidelines for Americans. We, therefore, examined the association of milk consumption and vitamin D status in the United States (US) population. Twenty-four-hour dietary recall data and serum 25(OH)D concentrations were obtained from the National Health and Nutrition Examination Survey 2001–2010 and were analyzed by linear and logistic regression after adjusting for anthropometric and demographic variables. Significance was set at p < 0.05. Approximately 57–80% children and 42–60% adults were milk consumers. Milk intake (especially reduced-fat, low fat and no-fat milk) was positively associated (p linear trend < 0.05) with serum vitamin D status and with a 31–42% higher probability of meeting recommended serum vitamin D (>50 nmol/L) levels among all age groups. Serum vitamin D status was also associated with both type and amount of milk intake depending upon the age and ethnicity. In conclusion, the results indicate that milk consumers consistently have higher serum vitamin D levels and higher probability of meeting recommended levels. Therefore, increasing milk intake may be an effective strategy to improve the vitamin D status of the US population.

Association between toenail zinc concentrations and incidence of asthma among American young adults: The CARDIA study

BackgroundAs an essential micronutrient, zinc plays an important role in modulating the immune system. However, data on the association between zinc concentrations and asthma incidence are sparse, especially in adults. MethodsWe prospectively followed up 3682 individuals aged 20–32 years without history of asthma or current asthma at baseline from 1987–1988 to 2015–2016. Zinc concentrations were measured in toenail clippings collected at Exam Year 2 using inductively-coupled-plasma mass spectroscopy. Asthma was diagnosed by a physician and/or reported medication use for asthma control with verification. Cox regression was used to model the association between toenail zinc concentrations and asthma incidence. ResultsOver an average of 22.5 years of follow-up, 508 incident cases of asthma were identified. After adjustment for potential confounders, no statistically significant association was found between zinc concentration and asthma incidence (HR = 0.81; 95% CI: 0.62, 1.07; Plinear trend = 0.26). The observed association was not materially modified by sex, body mass index, smoking or atopic status. When stratifying data by race, a significant inverse linear association was found among African Americans (per 1 standard deviation increment in toenail zinc concentrations: HR = 0.86; 95% CI: 0.75, 0.99; Plinear trend = 0.03), but not in Caucasians (HR = 1.07; 95% CI: 0.91, 1.25; Plinear trend = 0.42), though the test for interaction was not statistically significant (Pinteraction = 0.099). ConclusionsFindings from this prospective cohort study do not support a significant longitudinal association between toenail zinc concentrations and incidence of asthma among American young adults. Future studies are needed to confirm our findings.

Trends in Nutritional Status Evaluated by Nutritional Biomarkers Among US Adults

Background: Understanding trend in nutritional status is crucial to inform national health priorities to improve diets and reduce related diseases. However, limited data was available on the trend of nutritional status estimated by nutritional biomarkers. Methods: Trends in nutritional status evaluated by health nutritional biomarkers index (HNBI) score calculated based on nutritional biomarkers were analyzed among US adults in the National Health and Nutrition Examination Surveys (NHANES, 2003-2014). The lower the HNBI score, the healthier nutritional status would be. Findings: From 2003 to 2014, the estimated overall HNBI score decreased from 4.16 to 3.61 (P-linear trend < 0.001). The HNBI scores of vitamins and lipids decreased from 0.43 to 0.34 (P-linear trend = 0.012), and 2.17 to 1.78 (P-linear trend <0.001), respectively; while the HNBI score of proteins increased from 0.09 to 0.17 (P-linear trend < 0.001). No significant trend was found for the HNBI score of minerals (P-linear trend = 0.168). Participants aged 40-59 years, men, non-Hispanic blacks, and participants with low socioeconomic status accounted for the largest overall HNBI score compared to their comparts. Vitamin B6 and vitamin D, lead, cadmium, mercury, potassium, iodine, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, triglyceride, and total cholesterol were the main nutrients for these specific adults to be improved. Interpretation: The overall nutritional status was improved among US adults from 2003 to 2014 but some specific populations should be paid much attention to improve their nutritional status, including adults aged 40-59 years, men, non-Hispanic blacks, and participants with low socioeconomic status. Funding Statement: National Natural Science Foundation of China (Grant Numbers: 82073536 and 81573134). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: All respondents provided written informed consent. The NHANES protocols were approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board.

Prevalence, Awareness, Treatment, and Poor Control of Hypertension Among Young American Adults: Race-Stratified Analysis of the National Health and Nutrition Examination Survey

ObjectiveTo evaluate the race-stratified trends for prevalence, awareness, treatment, and control of hypertension in young American adults aged 18 to 44 years. Patients and MethodsThe National Health and Nutrition Examination Survey data from 2005–2016 for adults aged 18 to 44 years was used to calculate age-adjusted (using 2005, 2010, and 2015 US Census population proportions) weighted trends in prevalence, awareness, treatment, and control of hypertension among non-Hispanic white, non-Hispanic black, and Mexican-American participants as per the 2017 American College of Cardiology/American Heart Association guidelines. Trends were estimated by logistic regression models including demographic, socioeconomic, health care access, and Bonferroni correction for multiple comparisons as covariates. ResultsAmong 15,171 young American adults, stable trends for the prevalence, awareness, treatment, and control of hypertension was seen in all racial groups (Plinear trend>.05 for all). The prevalence from 2013 to 2016 was highest in non-Hispanic blacks (30.7%; 95% CI, 27.3 to 34.0%), followed by non-Hispanic whites (21.9%; 95% CI, 19.6 to 24.1%), and Mexican Americans (21.9%; 95% CI, 18.6 to 25.1%). The awareness was stable at ∼43.2% in non-Hispanic blacks, ∼34.8% in non-Hispanic whites, and ∼28.4% in Mexican Americans from 2005 to 2008 through 2013 to 2016. The stable treatment rates at nearly 34.4%, 23.7%, and 20.6%, were seen in non-Hispanic black, non-Hispanic white, and Mexican-Americans, respectively. The optimal control of hypertension was seen in 14.5% (95% CI, 12.1 to 17.0%) non-Hispanic blacks, 12.2% (95% CI, 10.3 to 14.0%) non-Hispanic whites, and 10.3% (95% CI, 7.1 to 13.5%) Mexican Americans from 2013 to 2016. ConclusionNearly one in every three non-Hispanic young black and one in every five young Mexican American and non-Hispanic white adults have hypertension. Our race-stratified analyses highlight the categorical need to improve the abysmal control of hypertension which is approximately 1 in 10 young adults.